Bone grafts are used in roughly two million orthopedic procedures each year, and general take one of three forms. Autografts, which typically consist of bone harvested from one site in a patient to be grafted to another site in the same patient, are the benchmark for bone grafting materials, inasmuch as these materials are simultaneously osteoconductive (serving as a scaffold for new bone growth), osteoinductive (promoting the development of osteoblasts) and osteogenic (containing osteoblasts which form new bone). However, limitations on the supply of autografts have necessitated the use of cadaver-derived allografts. These materials are less ideal than autografts, however, as allografts may trigger host-graft immune responses or may transmit infectious or prion diseases, and are often sterilized or treated to remove cells, eliminating their osteogenicity.
Given the shortcomings of human-derived bone graft materials, there has been a long-standing need in the field for synthetic bone graft materials. Synthetic grafts typically comprise calcium ceramics and/or cements delivered in the form of solid or granular implants, a paste or a putty. These materials are osteoconductive, but not osteoinductive or osteogenic. To improve their efficacy, synthetic calcium-containing materials have been loaded with osteoinductive materials, particularly bone morphogenetic proteins (BMPs), such as BMP-2, BMP-7, or other growth factors such as fibroblast growth factor (FGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and/or transforming growth factor beta (TGF-β). However, significant technical challenges have prevented the efficient incorporation of osteoinductive materials into synthetic bone graft substitutes which, in turn, has limited the development of high-quality osteoinductive synthetic bone graft materials.
One such challenge has been the development of a graft matrix which delivers an osteoinductive material over time, rather than in a single short burst release, and which has appropriate physical characteristics to support new bone growth. The generation of a material with appropriate physical characteristics involves, among other things, balancing the requirement that such materials be rigid enough to bear loads that will be applied to the graft during and after implantation with the requirements that they remain porous enough to allow for cell and tissue infiltration and may degrade or dissolve at a rate which permits replacement of the graft by new bone, and the separate requirement that they elute the osteoinductive material in a temporal and spatial manner that is appropriate for bone generation. It is only the combination of the above design criteria that will result in an optimal graft matrix for promoting new bone formation and ultimate healing. For example, BMP-eluting synthetic bone grafts currently available commercially do not meet one or more of these requirements, and a need exists for a bone graft material which is optimized for the delivery of osteoinductive materials such as BMPs.